Overall, the study showed that HPV has a substantial affect on overall survival in African-Americans with oropharyngeal cancer, Worsham and colleagues concluded.
Currently, the standard of care for HPV-positive head and neck cancer uses high-dose cis-platinum (Cisplatin), a chemotherapy drug that causes serious side effects that are difficult for patients to tolerate. The drug's toxicity raises the need for safer therapy, and, although further testing is necessary, combining CH1iB with a low dose of cis-platinum might one day provide an alternative, the researchers concluded.
High-risk types of human papillomavirus (HPV) are increasingly associated with oropharyngeal squamous cell carcinoma (OPSCC). However, HPV-positive OPSCC is highly curable, and patients with HPV have better survival compared with HPV-negative patients, whose cancers are usually associated with alcohol and tobacco use.
To better understand the molecular mechanisms underlying these differences, Jochen Hess, PhD, and colleagues at University Hospital Heidelberg monitored changes in DNA modifications in HPV-positive and HPV-negative OPSCCs (Journal of Clinical Investigation, May 1, 2013).
They applied an array-based approach to monitor global changes in CpG island hypermethylation between HPV-negative and HPV-positive OPSCCs, and identified a specific pattern of differentially methylated regions that critically depends on the presence of viral transcripts. This DNA modification pattern was significantly correlated with improved survival in three separate groups of OPSCC patients, the researchers noted.
Excerpts from an interview with Dr. Cohen
A report published in January in the Journal of the National Cancer Institute noted that the rate of HPV-related oropharyngeal cancers is rising, but there is no etiological data on what's causing the increase. What do you think is causing the increase?
We are still trying to figure that out, but there are some things we can be confident about and some things we have to surmise. We can be confident that the number of HPV-positive and tobacco-unrelated cancer patients are definitely increasing. Also, no doubt these are sexually transmitted entities and that HPV oropharynx cancer is a sexually transmitted disease. The epidemiology strongly favors that and there likely is an immune-host component to this -- the ability to eliminate the virus completely versus allowing the virus to integrate into DNA. What we do not know is why. Why are we seeing an increase in the incidence? Why do people not clear the virus? And in the subgroup of those patients, do they eventually develop cancer?
There is a parallel with oral herpes infections and the rise of HPV oropharynx cancer. There is a parallel with a change in sexual practices to more oral sexual activity versus other forms of sexual activity. And there is a parallel to a younger age of sexual activity where, because of concerns about contraception and sexually transmitted diseases, oral sexual activity may be preferred in younger individuals versus older people who are having sex to conceive.
Those may be demographic factors that are beginning to favor the emergence of HPV-positive cases. And, of course, these are things that have been going on for decades, not just now, because the virus takes 20 to 30 years to produce cancer. These are exposures that happened 20 years ago. They are trends that would parallel what we are seeing in terms of hosts that are not clearing the virus.
There may be modulating factors. We know that males are more likely to harbor the infection than females and that males have a much higher incidence -- a 3-to-1 ratio -- of HPV-related oropharynx cancer than females. There may be something hormone-related or differences in the immune systems that somehow protects females from developing oropharynx cancer. There may be an interaction with smoking, and some have cited an interaction with marijuana and the development of this cancer. How those may play a role in the ability of the immune system to clear this virus we still have to elucidate. But clearly there are host factors that in some individuals do not allow clearance of this virus, and we do not understand those completely.
Routine esophageal screening can increase the early detection of second primary esophageal squamous cell carcinoma and is particularly recommended for patients with head and neck squamous cell carcinoma (HNSCC), according to a study in JAMA Otolaryngology -- Head and Neck Surgery, March 21, 2013).
Patients with HNSCC have a high prevalence of second primary esophageal squamous cell carcinoma (ESCC), according to the study authors, from Chang Gung University College of Medicine in Taiwan. Some 5% to 15% of patients with HNSCC ultimately develop synchronous or consecutive ESCC, they noted.
Patients with HNSCC are also at risk of developing second primary neoplasms, particularly in the head and neck, lung, and esophagus. This has been attributed to "field cancerization" -- histologically abnormal epithelium adjacent to tumor tissue -- in the mucous membranes of these regions, likely from common exposure to tobacco, alcohol, and betel nut, according to the researchers.
The number of second primary tumors in Taiwan is far greater than in the U.S. or Europe, they added. Most of the Taiwan patients in this study drank alcohol, smoked, and chewed betel nut, which is considered a risk factor for developing esophageal cancer.
For this retrospective study, the researchers analyzed 3,053 newly diagnosed HNSCC patients at Kaohsiung Chang Gung Memorial Hospital between January 2004 and December 2010.
Following completion of treatment, all HNSCC patients were advised to have regular esophageal follow-ups every six months for three years. Patients in the study were divided into five categories based on tumor location: nasal cavity, oral cavity, oropharynx, larynx, or hypopharynx. They included 67 patients (2.2%) with nasal cavity cancer, 1,774 patients (58.1%) with oral cavity cancer, 514 patients (16.8%) with oropharyngeal cancer, 297 patients (9.7%) with laryngeal cancer, and 401 patients (13.1%) with hypopharyngeal cancer.
The patients were then divided into two groups based on whether or not they had received routine esophageal screenings, and the two groups were compared. In total, 1,592 patients had routine esophageal screening, and 1,461 patients did not.
The researchers found 115 second primary ESCC cases; of those, 44 were diagnosed in the nonroutine screening group, and 71 were diagnosed in the routine screening group.
The 115 patients with second primary ESCC were further analyzed. In the routine screening group, approximately 41% had an early T classification of ESCC, but in the nonroutine screening group, only about 20% had an early T classification; the difference between the groups was significant (p = 0.02).
The overall prevalences of second primary ESCC were 0.8% for the oral cavity, 6.2% for the oropharynx, 4.0% for the larynx, and 14.2% for the hypopharynx. Patients with oropharyngeal cancer, supraglottic cancer, transglottic cancer, and hypopharyngeal cancer (p < 0.001 for all) had a much higher risk of developing second primary ESCC.
The prevalence of second primary ESCC among the routine screening group (4.5%) was significantly higher than that among the nonroutine screening group (3.0%). Furthermore, the prevalence of second primary ESCC associated with oral cavity cancer cases among the routine screening group (1.2%) was significantly higher than that among the nonroutine screening group (0.3%).
Although the researchers found no significant differences at other sites of HNSCC between the two groups, they detected a trend toward a higher prevalence of second primary ESCC among the routine screening group in patients with laryngeal cancer (4.2% versus 3.8%), oropharyngeal cancer (6.5% versus 5.9%), and hypopharyngeal cancer (15.9% versus 12.3%).
"Therefore, patients with oropharyngeal, supraglottic, transglottic, and hypopharyngeal cancers should be aware of the possibility of esophageal lesions," the researchers wrote.
Gastric reflux increases the risk for laryngopharyngeal squamous cell carcinoma (LPSCC), but antacids may provide protection, according to a new study in Cancer Epidemiology, Biomarkers & Prevention (May 23, 2013).
U.S. researchers studied the incidence of gastric reflux and medication use in 631 Boston-area patients with LPSCC who were not heavy smokers or drinkers, matching them with 1,234 healthy controls.
After controlling for age, sex, race, smoking history, alcohol consumption, human papillomavirus (HPV) 16 infection, education, and body mass index, they found that people who had reported a history of frequent heartburn were 78% more likely to have cancer than those who did not. Those with frequent gastric reflux who took antacids reduced their risk for cancer by 41%, compared with those whose heartburn was untreated, according to lead author Scott Langevin, PhD, from Brown University, and colleagues.
There was no reduced risk among those taking proton pump inhibitors (e.g., Prilosec) or histamine H2 receptor antagonists (e.g., Zantac), but this may be because people taking such drugs are likely to have the most severe cases of acid reflux, and not because those drugs are ineffective, the researchers noted.
Spouses and long-term partners of patients with human papillomavirus (HPV)-related oral cancers appear to have no increased risk of oral HPV infections, according to a pilot study by researchers from Johns Hopkins University.
The study findings were presented June 1 at the 2013 American Society of Clinical Oncology annual meeting in Chicago.
The researchers noted that there are no guarantees that partners of such patients will not develop oral HPV infections or cancers, but the study found the partners had no increased prevalence of oral infections, which suggests their risk of HPV-related oral cancer remains low.
HPV-related oral cancers are rising in prevalence among white men in the U.S., and fear of transmitting the virus can lead to anxiety, divorce, and curtailing of sex and intimacy among couples, according to the researchers. Persistent oral HPV infections are a risk for developing oropharyngeal cancers.
At Johns Hopkins Hospital and three other hospitals, the study authors conducted surveys and took oral rinse samples from 166 male and female patients with HPV-related oropharyngeal cancers and 94 spouses and partners. The scientists also studied patients' tumor samples and performed visual oral examinations of spouses/partners. Of the 94 spouses/partners, six were male.
More than half of patients had at least one type of HPV DNA detectable in their oral rinses, including HPV16, the viral type most commonly associated with oral and other cancers. After a year, only seven patients (6%) still had oral HPV16 DNA detectable.
Of the 94 spouses/partners, six had oral HPV infections (6.5%). Among the six, none of the men and two of four females (2.3%) had HPV16 infections at very low levels. These infections were not detectable one year later. No oral cancers were detected among 60 spouses/partners who underwent a visual oral exam.
One spouse and one patient reported a history of cervical cancer. Two spouses reported a history of cervical precancer, and three patients said they had previous spouses with cervical cancers, but these were self-reported, unconfirmed cases.
More research is needed to determine the timeline of progression for HPV-related oral cancers and how HPV is transmitted and suppressed by the immune system, the study authors concluded.
Advaxis, a developer of immunotherapies for cancer and infectious diseases, has submitted an application for orphan drug designation with the U.S. Food and Drug Administration (FDA) for ADXS-HPV for the treatment of human papillomavirus (HPV)-associated head and neck cancer.
The orphan drug designation is granted to drug therapies intended to treat diseases or conditions that affect fewer than 200,000 people in the U.S. If granted, it entitles the sponsor to clinical protocol assistance with the FDA, plus federal grants, tax credits, and a seven-year market exclusivity period.
About 50,000 new cases of head and neck cancer are diagnosed annually, with about 15,000 deaths, Advaxis noted in a press release. HPV infection is estimated to account for 20% to 50% of current incidence. More than 80% of new cases occur in men, who are not typically part of HPV vaccination programs, according to the company.
ADXS-HPV is an immunotherapy that is designed to target cells expressing the HPV gene E7. Expression of the gene from high-risk HPV variants is responsible for the transformation of infected cells into dysplastic and malignant tissues. Eliminating these cells can eliminate the dysplasia or malignancy. ADXS-HPV is designed to infect antigen-presenting cells and direct them to generate a powerful, cellular immune response to HPV E7. The resulting cytotoxic T cells infiltrate and attack the tumors while specifically inhibiting tumor regulatory T cells and myeloid-derived suppressor cells in the tumors that are protecting it.
Data from a phase II study in recurrent cervical cancer showed that ADXS-HPV is an active treatment in this HPV-associated cancer, and Advaxis believes ADXS-HPV immunotherapy will show similar activity in HPV-associated head and neck cancer, given the shared causality of the cancers. The company has an ongoing phase I/II study in HPV-positive head and neck cancer in the U.K. and plans to initiate another in the U.S. in 2013.
Smokers and single men are more likely to acquire cancer-causing oral human papillomavirus (HPV), according to new results from the HPV Infection in Men (HIM) study (Lancet, July 2, 2013).
Researchers from Moffitt Cancer Center, the National Cancer Institute, Mexico, and Brazil also reported that newly acquired oral HPV infections in healthy men are rare and when present usually resolve within one year.
HPV-related oropharyngeal cancer is rare, but rates have been increasing rapidly, especially among men, the study authors noted. To determine the pattern of HPV acquisition and persistence in the oral region, they evaluated HPV infection status in oral mouthwash samples collected as part of the HIM study, which was originally designed to evaluate the natural history of genital HPV infections in healthy men.
"Some types of HPV, such as HPV16, are known to cause cancer at multiple places in the body, including the oral cavity," said lead author Christine Pierce Campbell, PhD, MPH, in a news release. "We know that HPV infection is associated with oropharyngeal cancer, but we don't know how the virus progresses from initial infection to cancer in the oral cavity."
During the first 12 months, nearly 4.5% of men in the study acquired an oral HPV infection. Less than 1% of men in the study had an HPV16 infection, the most commonly acquired type, and less than 2% had a cancer-causing type of oral HPV.
These findings are consistent with previous studies showing a low prevalence of oral HPV cancers, the researchers noted. However, the study suggests that the acquisition of cancer-causing oral HPV was greater among smokers and unmarried men.
Additional HPV natural history studies are needed to better inform the development of infection-related prevention efforts, the study authors concluded.